Proteomics of citrullination in cardiovascular disease

Citrullination is an enzymatic posttranslational modification (PTM), which has become a topic of recent research due to its involvement in various physiologic and pathologic processes. This review will focus primarily on the cardiovascular pathology associated to date with citrullination, including myocardial citrullination as well as the potential role of citrullination in atherosclerosis as a driver inflammation, especially in patients with rheumatoid arthritis (RA). There is extensive citrullination within normal and RA myocardium as well as the atherosclerotic plaque; and increased levels of antibodies to citrullinated proteins have been associated with increased cardiovascular burden in patients with RA. Given robust citrullination in both RA as well as non-RA patients, there also exists the potential for protein citrullination to contribute to cardiovascular pathology in the general population. However, to investigate this possibility will require development of improved biochemical and proteomic tools for the study of protein citrullination. The remainder of this review will discuss current and developing methodologies to study protein citrullination and discuss their applicability for the analysis of complex samples. The ability to identify and quantify citrullinated protein is a key to understanding the role of this PTM. Methodologies and limitations of current technology for the identification of citrullination are discussed.